This Program Project examines the developmental biology of human erythropoiesis. In Project I, we investigate methods of progenitor purification and the regulation of fetal hemoglobin synthesis in erythroblasts derived from progenitors. In Project V, we continue our study of the function of antibodies to specific regions of erythropoietin in an attempt to define the regions of the hormone that induce the replication and terminal differentiation of progenitor cells and define its receptor. In Project II, we begin a major new undertaking, the transfer of genes into hematopoietic progenitor cells, focusing on dihydrofolate reductase and adenosine deaminase as prototypes. In Project IV, we analyze the appearance of erythroid specific proteins on developing murine and human erythroid cells, with particular reference to the onset of expression of fibronectin receptors. In Project III, we study the pathophysiology of membrane disturbances in the thalassemia syndromes.